While Covid response has varied dramatically around the world, everyone has eagerly awaited a vaccine, with the hopes that life, travel, and the economy can return to normal. This week, one year after the initial outbreak, pharmaceutical companies have announced big breakthroughs.
Likely Covid Vaccine Candidates
Since late 2019, drug companies around the world have been in a frantic race to develop an effective vaccine for SARS-2, the virus that causes Covid. Vaccine research is being conducted by cellular and molecular biologists, biochemists, and microbiologists, in public and private labs that are a different type of front line on the pandemic. As of August 2020, there were more than nine Covid vaccine candidates in late-stage trials around the world. Here are the most promising candidates as of November:
- Pfizer. This week, Pfizer and BioNTech announced that their vaccine candidate, BNT162b2 demonstrated 95% efficacy with well-tolerated safety across a 43,000 person test group in a phase 3 trial. The most common side effects were fatigue (3.8%) and headache (2.0%).
- Moderna. Just days after Pfizer’s announcement, Moderna announced that their own candidate, MRNA-1273, was proven 94.5% effective in their own 30,000 person phase 3 trial.
- Russian vaccine. Meanwhile, in September, Russia was the first country to approve a vaccine against Covid-19. The Russian vaccine, named Sputnik V, claims 92% effectiveness. Health experts have some concerns about the Russian vaccine, because it was approved and administered before larger phase 3 trials had been completed, and the underlying data has not been available for international study and analysis. In September, this vaccine was administered to 10,000 high-risk volunteers from the health care industry, and in November it was administered to another 20,000 volunteers. From this data, the 90% efficacy rate has been estimated, while more in-depth study has covered just 20 Covid cases. Many people feel that this study group is too small to support the claims, and are waiting for Russia to release the full data from their phase 3 trial.
How do Covid Vaccines Work?
Current vaccines, including the SARS-2 vaccine, are developed using these common approaches:
- mRNA. Both the Pfizer and Moderna vaccines are mRNA vaccines. RNA vaccines have proven an exciting area of research in recent years, because they have shorter manufacturing times and greater effectiveness against rapidly evolving viruses like influenza. These vaccines introduce an mRNA sequence that is pre-coded for a specific antigen, directing the body’s immune system to defend against a specific pathogen. Because they don’t introduce infectious elements into the body, they are safer than traditional vaccines, and because they prime the immune system for the desired antigen, they are more effective. They are also faster and easier to produce, with laboratory production that is scalable for specific outbreaks and epidemics. RNA-based vaccines also pose some challenges: free RNA in the body is quickly broken down, so the mRNA strand has to be incorporated into a larger molecule for delivery. These larger particles or liposomes help to package and stabilize the strand. RNA vaccines also require cold storage, which can be a challenge in remote regions without reliable access to refrigeration.
- Adenovirus vector. The Russian vaccine is an adenovirus vaccine, as is the vaccine being developed by China’s CanSino and American drug company Johnson & Johnson. Adenovirus vaccines use genetically modified viruses to stimulate an immune response without using actual infectious agents. The engineered viruses simulate the protein structure of an infected cell, triggering B and T cell production to destroy the virus. This method of vaccine production relies on using a widely available virus, which can be created and then used to host a wide range of specific vaccines. For this reason, adenovirus vaccines are fast and affordable to produce. However, once the body develops antibodies for the virus, subsequent vaccines or boosters become less effective; adenovirus immunity lasts for a long time, and if a person is immune to the host-virus, they may not get the benefit of the vaccine. The presence of existing antibodies in recipients can vary widely, which affects the efficacy of the vaccine. The Russian vaccine relies on a two-step system: a vaccine delivered by the rarer Ad26 vector, followed by a booster with the more common Ad5, but the immune response to these vectors varies widely in different regions around the world.
- Inactivated virus. An inactivated virus vaccine is the traditional vaccine many of us are accustomed to. These vaccines are created by disabling the disease-causing capability of the pathogen, and then using this living-but disabled pathogen to trigger an immune response. The immune response to inactivated virus tends to be weaker than for active viruses, so repeated booster shots may be necessary. These types of the virus also pose a greater risk for people with weakened immune systems. This week, Sinovac Life Sciences in China released the results of their phase 2 trials of a vaccine based on an inactivated SARS-CoV-2 virus. Among the 600 participants, neutralizing antibodies were seen in 92% of participants who received an initial 3 μg dose, while 98% of the 6 μg group had antibodies, increasing to 98% and 100% respectively after 28 days. However, 33% of the 3 μg and 35% of the 6 μg group reported adverse side effects. China’s CoronaVac is now headed to phase 3 trials with the 3 μg dosage.
During testing and trials, data science becomes as critical as medical science on the road to an effective vaccine. Advanced analysis is needed not just to determine whether a vaccine is effective, but to determine whether it is safe, and begin anticipating methods for manufacturing and engineering on a larger scale.
Paths to Distribution
Once a vaccine is approved, the next challenge is just beginning. Not only will billions of doses of the vaccine need to be produced, but they will need to be quickly deployed all over the world. Distributing and administering a vaccine in the midst of a pandemic poses a huge challenge for the world’s logistics and shipping channels, especially in remote regions with reduced infrastructure. Generally speaking, public health experts begin by determining which populations should be prioritized for vaccine access. Health departments have spent the past year mapping various scenarios, planning for initial targeted administration for priority populations, including identifying administration sites with the capacity for storing, handling, and administering a vaccine. Administration sites also need a variety of basic PPE, medical, and sanitation supplies.
Over time, as vaccine supply ramps up, distribution needs to ramp up accordingly, with access for the general public through a wide distribution network. Eventually, the vaccine will also need to be distributed to remote and less accessible areas.
Throughout the distribution process, extensive monitoring is required. Drug companies as well as public health experts will be closely monitoring outcomes, being attentive to adverse effects, the potential need for follow-up doses, and identifying any rare side effects not identified in clinical trials, which are more closely controlled and monitored. Pharmacovigilance is especially critical during the Covid pandemic, because it is likely that vaccines will be distributed without the kind of longitudinal studies many drugs undergo before approval.
Challenges and Unknowns of a Covid Vaccine
While all vaccines carry a certain amount of health risk, a Covid vaccine faces a set of unique challenges. Here are a few of the things we simply don’t know yet:
- Transmission risk. All of our viable Covid vaccine candidates have been shown to be effective at reducing Covid infection. However, we still have little data about how these vaccines affect Covid transmission rates, which may be especially important early in the process, before a vaccine has been widely distributed.
- Public scepticism. There are significant percentages of the population in the US in particular who do not believe in vaccines, or who do not believe in Covid, or who believe other misinformation or conspiracy theories. These people may refuse to accept a vaccine, which may pose unusual challenges for public health.
- Liability questions. While it is still sheer speculation, some legal experts are already raising questions of liability if a vaccine is rushed to market with abbreviated time for study and research. A vaccine that is insufficiently studied may have previously unknown side effects, and in a time of already limited and strained public trust, vaccine problems could become catastrophic. The US and EU have very different approaches to vaccine liability, with the US developing a “no-fault” compensation plan, and the EU pursuing shared and limited liability programs.
The world eagerly awaits a Covid vaccine, and pharmaceutical companies have risen to the challenge in record time. The extraordinary circumstances of the Covid pandemic have demanded extraordinary solutions, and there is still a need for an army of scientists, researchers, data analysts, engineers, public health experts, and front-line medical workers. If you are passionate about solving problems and saving the world, contact grapefrute for help finding your place in the fight.